Forty patients with advanced solid tumors of diverse primary sites received a combination of cyclophosphamide (1 gm/m2), cytosine arabinoside (300 mg/m2), and methotrexate (80 mg/m2) given intermittently at 2-3-week intervals. Eight of the 40 patients received citrovorum factor rescue. The major limitation of therapy was suppression of bone marrow elements. Only minimal nonhematologic toxicity was encountered. Granulocytes appeared the most sensitive. The first course of treatment produced median nadir granulocyte and platelet counts of 1200 and 100,000 cells/mm3 respectively. Subsequent courses were tolerated with no evidence of increasing myelosuppression. Objective antitumor responses were noted in five of 16 patients with lung cancer and in eight of 14 women with breast cancer with a median duration of 8 months.